Background: The association of the -675 4G/5G polymorphism of the plasminogen activator inhibitor-1 (PAI-1) gene with cardiovascular disease in patients with type 2 diabetes (T2DM) is unknown.
Methods: Genotyping was performed in 672 consecutive Caucasian patients undergoing coronary angiography for the evaluation of stable coronary artery disease (CAD). Vascular events were recorded over 4 years.
Results: In non-diabetic subjects (n=524), the homozygous PAI-1 4G4G genotype was significantly associated with significant coronary stenoses>or=50% (adjusted odds ratio (OR) OR=1.84 [1.17-2.92]; p=0.009); however, in T2DM patients (n=148) no such association was observed (OR=0.67 [0.26-1.71]; p=0.401). An interaction term T2DMx4G4G genotype was significant (p=0.006), indicating a significantly stronger association of the polymorphism with CAD in non-diabetic subjects than in patients with T2DM. Also prospectively, the 4G4G genotype conferred an increased risk of vascular events in non-diabetic subjects but not in T2DM patients (hazard ratios 1.76 [1.13-2.74]; p=0.014 and 0.68 [0.30-1.54]; p=0.360, respectively). Again, the interaction T2DMx4G4G genotype was significant (p=0.018).
Conclusions: Presence of T2DM significantly modulates the vascular risk conferred by the PAI-1 -675 4G/5G polymorphism in angiographied coronary patients.